EPIDEMIOLOGY, PATHOGENESIS AND DETERMINANTS OF HIV-1 TRANSMISSION AND DISEASE PROGRESSION IN THE ANGOLAN PERINATAL HIV COHORT APEHC

Funder

Organizational Unit

Publications

Predictors of attrition and immunological failure in HIV-1 patients on highly active antiretroviral therapy from different healthcare settings in mozambique

Publication . Palladino, Claudia; Briz, Veronica; Bellón, José María; Bártolo, Inês; Carvalho, Patrícia; Camacho, Ricardo; Muñoz-Fernández, M. Ángeles; Bastos, Rui; Manuel, Rolanda; Casanovas, José; Taveira, Nuno

In Mozambique, the evaluation of retention in HIV care and ART programmes is limited. To assess rate and predictors of attrition (no retention in care) and HAART effectiveness in HIV-1 infected patients who pay for medication and laboratory testing in Mozambique, we conducted a multicenter survey of HIV-1-infected patients who started HAART during 2002–2006. Cox proportional hazard models were used to assess risk of attrition and of therapy failure. Overall, 142 patients from 16 healthcare centers located in the capital city Maputo were followed-up for 22.2 months (12.1–46.7). The retention rate was 75%, 48% and 37% after one, two and three years, respectively. Risk of attrition was lower in patients with higher baseline CD4 count (P = 0.022) and attending healthcare center 1 (HCC1) (P = 0.013). The proportion of individuals with CD4 count ≤200 cells/µL was 55% (78/142) at baseline and decreased to 6% (3/52) at 36 months. Among the patients with available VL, 86% (64/74) achieved undetectable VL levels. The rate of immunologic failure was 17.2% (95% CI: 12.6–22.9) per 100 person-years. Risk of failure was associated to higher baseline CD4 count (P = 0.002), likely reflecting low adherence levels, and decreased with baseline VL ≥10,000 copies/mL (P = 0.033). These results suggest that HAART can be effective in HIV-1 infected patients from Mozambique that pay for their medication and laboratory testing. Further studies are required to identify the causes for low retention rates in patients with low CD4 counts and to better understand the association between healthcare setting and attrition rate.

2013Journal article

Open access

Off-label use of rilpivirine in combination with emtricitabine and tenofovir in HIV-1-infected pediatric patients A multicenter study

Publication . Falcon-Neyra, Lola; Palladino, Claudia; Gomez, María Luisa Navarro; Soler-Palacin, Pere; Gonzalez-Tome, María Isabel; De Ory, Santiago J.; Frick, Marie Antoinette; Fortuny, Clàudia; Noguera-Julian, Antoni; Moreno, Elena Bermúdez; Santos, Juan Luis; Olbrich, Peter; López-Cortés, Luis F.; Briz, Verónica; Neth, Olaf

To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/μL (uVL, P = 0.069) and 480 to 830/μL (dVL, P = 0.051). Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children.

2016Journal article

Open access

Prevalence of relevant NS5A resistance-associated substitutions to elbasvir in genotype 1a hepatitis C virus patients in Spain

Publication . Palladino, Claudia; Esteban-Cartelle, Beatriz; Maté-Cano, Irene; Sánchez-Carrillo, Marta; Resino, Salvador; Briz, Verónica

Resistance-associated substitutions (RASs) to the new HCV NS5A inhibitor elbasvir may limit its efficacy and lead to virological failure in HCV-GT1a-infected patients. There are no data outside clinical trials evaluating their prevalence and impact in grazoprevir/elbasvir in GT1a-infected patients in Spain. A multicentre cross-sectional study of 632 initial patients was conducted. In 13 of these patients, the sample could not be amplified or a consensus sequence by Sanger sequencing could not be performed. Ultimately, 617 HCV-G1a-infected individuals treated at 84 Spanish hospitals from the 17 autonomous communities plus the 2 autonomous cities of Spain were analysed. HCV population sequencing was used to identify RAS to elbasvir and the mutational pattern and drug sensitivity were confirmed by geno2pheno[HCV]. Viruses bearing RASs to elbasvir were present in 6.2% of HCV-G1a infected patients. The most common RASs were the Y93C/H/N and Q30E/H/R (2.4% and 2.3%, respectively). Only 3.4% of the identified RASs to elbasvir conferred reduced susceptibility to elbasvir by geno2pheno[HCV], which exclusively identified the positions Q30H/R (n = 7) and Y93C/H/N (n = 8) as single mutations and Q30H + Y93H (n = 4) and Q30R + Y93H (n = 2) as double mutations as the major RASs to elbasvir. A lower prevalence of RASs to elbasvir was observed in our HCV-G1a Spanish cohort than reported previously in clinical trials evaluating patients from the USA. This information may be essential to guide the implementation of grazoprevir/elbasvir in Spain and to manage G1a-infected patients.

2018Journal article

Restricted access

Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Publication . Palladino, Claudia; Ezeonwumelu, Ifeanyi J.; Marcelino, Rute; Briz, Verónica; Moranguinho, Inês; Serejo, Fátima; Velosa, José Fernando; Marinho, Rui; Borrego, Pedro; Taveira, Nuno

Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour among the different genotypes. Here, we performed the first characterization of the epidemic history and transmission dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on 230 direct-acting antiviral drugs (DAA)-treatment naïve patients in Lisbon. Phylogenetic analysis was used for subtyping and transmission cluster identification. Bayesian methods were used to reconstruct the epidemic history of HCV subtypes. Sequences were analysed for resistance-associated substitutions (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a) and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting multiple introductions of the different subtypes in this population. Five distinct epidemics were identified. The first significant HCV epidemic in Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b and was likely associated with blood transfusions. Rapid expansion of GT3a occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug use. The most recent epidemics were caused by GT4a and GT4d and seem to be associated with the resurgence of opioid use. The C316N substitution was found in 31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and undergoing dasabuvir-based regimens will be important to determine its impact on treatment outcome.

2018-12Journal article

Open access

Early infant diagnosis of HIV-1 infection in Luanda, Angola, using a new DNA PCR assay and dried blood spots

Publication . Martin, Francisco; Palladino, Claudia; Mateus, Rita; Bolzan, Anna; Gomes, Perpetua; Brito, José; Carvalho, Ana Patrícia; Cardoso, Yolanda; Domingos, Cristovão; Clemente, Vanda Sofia Lôa; Taveira, Nuno

Background Early diagnosis and treatment reduces HIV-1-related mortality, morbidity and size of viral reservoirs in infants infected perinatally. Commercial molecular tests enable the early diagnosis of infection in infants but the high cost and low sensitivity with dried blood spots (DBS) limit their use in sub-Saharan Africa. Objectives To develop and validate a sensitive and cheap qualitative proviral DNA PCR-based assay for early infant diagnosis (EID) in HIV-1-exposed infants using DBS samples. Study design Chelex-based method was used to extract DNA from DBS samples followed by a nested PCR assay using primers for the HIV-1 integrase gene. Limit of detection (LoD) was determined by Probit regression using limiting dilutions of newly produced recombinant plasmids with the integrase gene of all HIV-1 subtypes and ACH-2 cells. Clinical sensitivity and specificity were evaluated on 100 HIV-1 infected adults; 5 infected infants; 50 healthy volunteers; 139 HIV-1-exposed infants of the Angolan Pediatric HIV Cohort (APEHC) with serology at 18 months of life. Results All subtypes and CRF02_AG were amplified with a LoD of 14 copies. HIV-1 infection in infants was detected at month 1 of life. Sensitivity rate in adults varied with viral load, while diagnostic specificity was 100%. The percentage of HIV-1 MTCT cases between January 2012 and October 2014 was 2.2%. The cost per test was 8-10 USD which is 2- to 4-fold lower in comparison to commercial assays. Conclusions The new PCR assay enables early and accurate EID. The simplicity and low-cost of the assay make it suitable for generalized implementation in Angola and other resource-constrained countries.

2017Journal article

Open access